MiR-149-5p in Tfh Cell-Derived Exosomes Promotes B Cell Proliferation and Maturation Through the Wnt3a/Axin2 Axis in Allergic Rhinitis

Abstract

Allergic rhinitis (AR) is one of the most frequently observed diseases in otorhinolaryngology, a global issue that alters the quality of life of patients. Both B cells and follicular helper T cells (Tfhs) have important roles in allergic diseases. However, how Tfhs and B cells interact to modulate allergic rhinitis pathogenesis remains unclear. In this study, two models of allergic rhinitis were examined, including the co-culture of follicular helper T cells (Tfhs) isolated from mouse spleen with B cells. To further define the mechanism, exosomes from Tfh cells were isolated and added to B cells. Bulk RNA sequencing (RNA-seq) analysis was used to compare exosomes derived from Tfhs cells in a mouse model of allergic rhinitis and exosomes derived from Tfhs cells in wild-type mice. Among them, miR-149-5p was observed to be lowly expressed in the allergic rhinitis group, which was confirmed using qPCR. miR-149-5p mimics or inhibitors were utilised to overexpress or knock down miR-149-5p in Tfhs, which were then co-cultured with B cells, demonstrating that miR-149-5p is negatively correlated with B cell proliferation and maturation. The function of WNT3A, a target gene of miR-149-5p, and the downstream effector AXIN2 on the proliferation and maturation of B cells were predicted and verified. We show that miR-149-5p packaged in Tfhs-derived exosomes induces B cell proliferation and maturation through the WNT3A/AXIN2 axis. The discovery will contribute to new ideas for the treatment of allergic rhinitis.